The purpose of this study is to test the safety of vorinostat (Zolinza) and azacitidine (Vidaza) when combined with gemtuzumab ozogamicin (GO) at different dose levels. These drugs increase the effect of GO against leukemia cells in the test tube, but we don't know yet whether they also increase the anti-leukemia effect of GO in people.

A Phase 1/2 Study of Vorinostat (Zolinza®) in Combination With Gemtuzumab Ozogamicin (Mylotarg®) and Azacitidine (Vidaza®) in Patients 50 Years of Age and Older With Relapsed/Refractory Non-APL Acute Myeloid Leukemia (AML)

Efficacy Defined as Best Response Achieved During Study Treatment Measured by Complete Remission (CR) Rate [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Relapse-free Survival (RFS) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Estimated using Kaplan-Meier method. Logistic regression will be used as a tool to assess the association of various factors with the probability of response, recognizing that the power to detect statistically significant associations will be limited due to the sample size (and expected number of responses). The impact of remission and post-remission therapy on RFS will be assessed using Cox regression with remission and therapy treated as time-dependent covariates.

OUTLINE: This is phase I, dose-escalation study of vorinostat followed by a phase II study.

Patients receive vorinostat orally (PO) on days 1-9, azacitidine subcutaneously (SC) or intravenously (IV) over 10-40 minutes on days 1-7, and gemtuzumab ozogamicin IV over 2 hours on day 4 and 8. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 3 years.

Eligibility

Ages Eligible for Study:

50 Years and older (Adult, Senior)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Prior morphological diagnosis of acute myeloid leukemia (AML) other then acute promyelocytic leukemia (APL) according to the 2001 WHO criteria; patients with biphenotypic AML are eligible

Need for first salvage chemotherapy for persistent or relapsing disease, defined by standard criteria, after at least one course of conventional chemotherapy

A bone marrow biopsy is not required but should be obtained if the aspirate is dilute, hypocellular, or not aspirable; outside marrow exams performed within the stipulated time period are acceptable if the slides are reviewed at the study institution

Patients with symptoms/signs of hyperleukocytosis or WBC > 100,000/uL can be treated with leukapheresis prior to enrollment

Collection of bone marrow and peripheral blood specimens for correlative studies prior to study treatment is highly recommended; peripheral blood only is acceptable if the peripheral blast count is > 5,000/uL and > 50% of total WBC

Must agree to use adequate contraception prior to and during the study

Can understand and sign a written informed consent document; a legally authorized representative can provide consent if the patient is unable

Exclusion Criteria:

Remission or second or later relapse

Diagnosis of another malignancy, unless diagnosed at least 2 years earlier and disease-free for at least 6 months after completion of curative intent therapy except:

Organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values if hormonal therapy has been initiated or a radical prostatectomy was performed

Refractory/relapsing blast crisis of chronic myeloid leukemia (CML)

Prior anti-AML treatment with GO, histone deacetylase (HDAC) inhibitor (including the use of valproic acid for control of seizure activity or other purposes), or demethylating agent

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00895934